The goal of this project is to learn more about the control of movement in normal humans and in patients with voluntary movement disorders such as Parkinson's disease, cerebellar ataxia, hemiplegia from stroke and dystonia. The tools we use include clinical neurophysiological methods such as electroencephalography, electromyography, and transcranial magnetic stimulation (TMS) and neuroimaging with positron emission tomography and functional magnetic resonance imaging (fMRI). Currently active projects in the Section include studies of normal physiology, the pathophysiology and treatment of dystonia, the bradykinesia in Parkinson's disease, treatment of ataxia, and studies of recovery from hemiplegia. Functional magnetic resonance imaging (fMRI) was used to investigate the influence of normal aging on automatic movements. Previously, we have studied younger persons, and we intend to study patients with Parkinson's Disease next. Older subjects were asked to practice sequential finger movement tasks until they could perform them automatically. Our results showed that after extensive training, most aged healthy subjects can achieve automaticity, but with more activity in the SMA, cerebellum, dorsal prefrontal cortex, premotor area, caudate nucleus and occipital cortex compared to young subjects during similar movements. We are also studying postural instability and its changes with aging, given the importance of falls in the elderly. We are pursuing the hypothesis that neural detectors of unstable postures deteriorate with aging. We have evidence for these neural detectors with both EEG and fMRI studies. Voluntary movements are either triggered or self initiated. Pursuing the hypothesis that there is a shared neural network that is activated with different types of triggered movements, using fMRI we showed such a network in the right posterior superior temporal cortex, right dorsal premotor cortex, left inferior frontal cortex, cerebellar vermis, and SMA. In another study, we are trying to determine methods using EEG to predict in real time when someone is going to move and whether they will move their right or left hand. From offline studies, we found two significant factors of the power changes on the two hemispheric primary motor areas that can predict movement intention and classify left hand movement from right hand movement. Simple movements have been studied for many years, but most movements humans make are more complex. We are now studying complex praxis movements with both EEG and fMRI. Coherence analysis with EEG has shown that parietal and premotor areas are coherent during preparation and execution of movement inferring event related functional connectivity. We have been doing many studies of dystonia largely in patients with focal hand dystonia. We have completed a survey of "tricks" that patients use to reduce their dystonia in preparation for physiological studies of the mechanism of tricks. We used voxel-based morphometry to demonstrate a robust increase in grey matter in the hand representation of perirolandic cortices, bilaterally, in these patients. We have devoted considerable time in pursuing the hypothesis that there is a deficient surround inhibition with voluntary movement in dystonic patients. We have demonstrated this with transcranial magnetic stimulation (TMS). We are now pursuing the mechanism of surround inhibition studying different types of known inhibitory processes. We are also using EEG methods to see if this will help reveal surround inhibition mechanisms. In the area of Parkinson's Disease, we have been developing a raclopride PET method to assess striatal dopamine release during implicit motor learning. We are also exploring whether abnormal dopamine release in Parkinson's Disease will influence normal patterns of brain connectivity as assessed with EEG coherence. We are evaluating the efficacy of high frequency repetitive TMS to improve the speed of gait and hand movements in patients with Parkinson's Disease in a placebo controlled trial. We completed a double-blind placebo control trial evaluating the efficacy of IVIg in patients with ataxia associated with antigliadin antibodies (gluten sensitive ataxia). Preliminary evaluation suggests that IVIg may be useful in patients with elevated IgG antigliadin antibodies, but the effect is transient. Patients with elavated IgA antigliadin antibodies appeared not to have any response to the treatment. Following the observation that there is an improvement of hand function in chronic stroke after local anesthesia of the upper part of the paretic arm, we are now trying to confirm these findings in a controlled study design. We are developing tasks to ascertain characteristics of motor cortex physiology in healthy children during normal maturation with the goal of understanding anomalous motor cortex physiology in children with cerebral palsy. We have performed EEG studies in children and adults during bimanual and unimanual finger tapping to determine maturation of inter- and intra-hemispheric coherence during motor tasks, motor learning studies to determine maturation of bimanual and unimanual procedural learning, and TMS studies to determine maturation of stimulus response curves.